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OMM alters chronic ethanolinduced changes to VTA GABA neurons, NAc DA release and measures of withdrawal in rats

Journal: Journal of Osteopathic Medicine Date: 2021/12, 121(12):Pages: A45-A46. doi: Subito , type of study: animal experiment

Full text    (https://www.degruyter.com/document/doi/10.1515/jom-2021-2000/html)

Keywords:

alcohol [11]
animal experiment [67]
brain [106]
drugs [26]
OMT [3752]
opioids [40]
osteopathic manipulative treatment [3772]

Abstract:

Context: Emerging mechanistic data suggests that stimulation to spinal mechanoreceptors may be effective in the treatment of opioid and ethanol-use disorders by modulating brain regions involved in chronic drug exposure.1 2 3 These modulations include robust changes in the mesolimbic circuitry.4 5 These data underlie the import of evaluating potential effects of osteopathic manual manipulation on the mesolimbic circuitry. Objective: Frequency specific tissue displacement, as a reproducible analogue to cervical spine OMM (termed ‘OMMa’), in rodents has been used to modify neuronal GABA activity in the ventral segmental area (VTA) and dopamine (DA) release in the nucleus accumbens (NAc).4,5 To determine whether OMMa to the cervical spine can ameliorate the effects of ethanol-induced changes to VTA GABA neurons, DA release in the NAc and behavioral measures of withdrawal in rats. Methods: In this mechanistic original research we randomly assigned Wistar rats to one of four groups, saline no OMMa, saline OMMa, ethanol no OMMa and ethanol OMMa. Groups were given isovolumetric injections of ethanol (2.5 mg/kg; IP) or saline and either given OMMa or sham. OMMa was administered by a surgically implanted mechanical stimulation device adjacent to the right C3-7 laminae. Intervention was given immediately following injection 2x/day for 7 days to induce dependence. 24-hours post final injection, during withdrawal, behavioral assays were performed. Dopamine release and GABA neuron firing was measured during withdrawal following a reinstatement dose of ethanol (2.5mg/kg; IP) with microdialysis and single unit electrophysiology respectively. Data were analyzed using ANOVA followed by Tukey post hoc analyses. The purpose of this study was to determine a mechanistic rationale for potential human testing of OMM in the treatment of alcohol use disorder. Results: We show that when OMMa is administered concurrently with alcohol, it alters alcohol-induced desensitization of VTA GABA neuron firing rate in response to a reinstatement dose of ethanol (2.5mg/kg;IP) from 117.5 % of baseline to 32.3 %. Dopamine release in the NAc at 20 min post-injection was changed from 95.4% of baseline to 144.4 % and at 80 min from 104.1% to 138.2%. Further, behavioral indices of withdrawal (rearing, open-field crosses, tail stiffness, gait and elevated-plus times) were substantively ameliorated with concurrent OMMa treatment. Conclusion: These data suggest a possible role for the use of OMM in the treatment of alcohol and opioid-use disorders. However, further studies are needed to evaluate hodological underpinnings of the findings presented and to evaluate proper frequency and timing of potential treatments. In all, this study demonstrates that further study in this area is indicated.


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